Eps8 in the midst of GTPases
Eps8 in the midst of GTPases
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DOI：
10.1016/s1357-2725(02)00064-x
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发表时间：
2002-10-01
影响因子：
4
通讯作者：
Scita, G
中科院分区：
文献类型：
--
作者：
Di Fiore, PP;Scita, G
Eps 8最初被鉴定为表皮生长因子受体（EGFR）激酶活性的底物，显示出典型的信号分子结构域组织，包括推定的N-末端PTB结构域、中心SH 3结构域和C-末端“效应区”。后一个区域指导Eps 8在细胞内的定位，并且足以激活GT3，Rac，导致肌动蛋白细胞骨架重塑。Eps 8通过其SH 3结构域与Abil（也称为E3 b1）或RN-tre结合。Abi 1将Eps 8和Sos 1（Ras和Rac蛋白的双特异性鸟嘌呤核苷酸交换因子）结合在一起，从而促进三聚体复合物的形成，而三聚体复合物又是激活Rac所需的。另一方面，RN-tre，Rab 5 GT3激活蛋白，通过进入与Eps 8的复合物，抑制EGFR内化。此外，RN-tre与Abi 1竞争结合Eps 8，使后者从其Rac激活功能中转移。因此，根据其在不同复合物中的参与，Eps 8通过Rac参与EGFR信号传导，并通过Rab 5参与内吞作用。(C)2002爱思唯尔科技有限公司版权所有。
Eps8, originally identified as a substrate for the kinase activity of the epidermal growth factor receptor (EGFR), displays a domain organization typical of a signaling molecule that includes a putative N-terminal PTB domain, a central SH3 domain, and a C-terminal "effector region". This latter region directs Eps8 localization within the cell and is sufficient to activate the GTPase, Rac, leading to actin cytoskeletal remodeling. Eps8 binds, through its SH3 domain, to either Abil (also called E3b1) or RN-tre. Abi1 scaffolds together Eps8 and Sos1, a dual specificity guanine nucleotide exchange factor for Ras and Rac proteins, thus facilitating the formation of a trimeric complex, in turn required for activation of Rac. On the other hand, RN-tre, a Rab5 GTPase activating protein, by entering in a complex with Eps8, inhibits EGFR internalization. Furthermore, RN-tre competes with Abi1 for binding to Eps8, diverting the latter from its Rac-activating function. Thus, depending on its engagement in different complexes, Eps8 participates to EGFR signaling through Rac and endocytosis through Rab5. (C) 2002 Elsevier Science Ltd. All rights reserved.